Continuing efforts will be made to use: 1) intermediary metabolism in pregnancy as a model system for evaluating regulation in the fed and fasted state; and 2) phosphorus metabolism during stimulation of secretory structures (particularly pancreatic islets) to define some of the molecular changes that characterize the transition from "rest" to "work." Studies in pregnancy will attempt to integrate contributions from multiple systems via kinetic analysis of alanine and glucose turnover in intact rats and metabolic characterization of isolated hepatocytes. Efforts to determine factors which influence perinatal and neonatal events will be extended in acute and longitudinal studies of pregnant humans. Particular attention will be directed to the effects of gravidity on the cyclical excursions of maternal fuels and hormones. Investigations into phosphorus metabolism and the induction of "work" will concentrate on a) the rapid transient efflux of orthophosphate-32P from prelabeled isolated pancreatic islets which we have shown to constitute a new index of secretory stimulation (the "phosphate flush"); and b) the turnover of phosphatidylinositol. Efforts will be made to correlate the "phosphate flush" with flux of other ions such as calcium and to document pathways of phospholipogenesis. Attempts will be made to localize the "phosphate flush" and phosphatidylinositol metabolism in the sequence of stimulus-secretion coupling in the hope that these phenomena may be developed into new biochemical probes for dissecting the "work" response.